No abstract

SummaryThe scaffold protein caspase recruitment domain-containing protein 11 (CARD11) is implicated in the regulation of inflammation and autoimmunity. The present study aimed to explore the role of CARD11 in the pathogen-

A novel iridium-catalyzed ring-opening reaction of azabicyclic alkenes with a variety of primary aromatic amines is reported, which afforded the corresponding 1,2-trans-diamine derivatives in high yields (up to 96%) with excellent enantioselectivities (up to 97% ee) under relatively mild conditions. The trans configuration of product 2b was confirmed by X-ray crystallography.Transition-metal-catalyzed asymmetric ring-opening (ARO) reactions have been demonstrated to be useful methods for the synthesis of chiral building blocks. 1 Many ARO reactions offer excellent enantioselectivities, such as the palladium-catalyzed ARO reactions of organoboronic acids, 2 the nickel-catalyzed conjugate addition of terminal alkynes, 3 the copper-catalyzed ARO reactions of Grignard reagents 4 and aluminum reagents, 5 the rhodium-catalyzed ARO reactions of phenol, 6 and various metal-catalyzed ARO reactions of dialkylzincs. 7 Those reactions provide potential promising methods to form carbon-nitrogen bonds through the addition of nitrogen-based nucleophiles to the azabicyclic alkenes, offering facile and efficient synthetic routes to 1,2-trans-diamino derivatives. Compounds possessing a 1,2-trans-diamino skeleton have many potential applications in both chemistry and medicine. 8 In addition, the catalytic addition of amines to unsaturated bonds has attracted great attention in organic synthesis because of its high atom efficiency. 9 Recently, ARO of oxa-and azabicyclic alkenes with nitrogen-based nucleophiles catalyzed by rhodium and iridium complexes has been reported by Lautens et al. 10a-e and our laboratory, 10f-k respectively. Herein, we report the extension of this method to asymmetric ring-opening reactions of the less reactive azabicyclic alkenes 1a-c with primary aromatic amines to afford the corresponding cyclohexyl 1,2-transdiamine derivatives in good to excellent enantioselectivities in the presence of iridium catalysts.

Left atrial (LA) fibrosis is a major arrhythmogenic substrate for atrial fibrillation (AF). The purpose of this study was to assess whether isoproterenol (ISO) induces LA fibrosis and increases susceptibility to AF, exploring the underlying mechanisms. Male Sprague-Dawley rats were subcutaneously injected ISO once per day for 2 days. Five weeks after injection, the ISO group had higher susceptibility AF and prolonged AF duration compared with the control group. ISO decreased LA conduction velocity (CV) and increased LA conduction heterogeneity. ISO increased fibrosise areas and the protein levels of collagen types I and III in the left atrium. Antifibrosis drug pirfenidone decreased AF occurrence and reduced LA fibrosis in ISO treated rats. ISO injection induced atrial ischemia infarction by increasing heart rate and decreasing diastolic and systolic blood pressures. These findings demonstrated that ISO increases susceptibility to AF by increasing LA fibrosis and LA conduction abnormalities 5 weeks after injection. ISO injection induces atrial ischemic injury is the main cause of fibrosis. Rats with ISO-induced LA fibrosis may be used in further AF research.

Brachial plexus root avulsion (BPRA) leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av) treated with normal saline), Av+GM1 (treated with monosialoganglioside), and control. At time points of 3 day (d), 1 week (w), 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.